General concepts of microvascular flow and volume have been elucidated but the events in individual series and parallel circuits have not been defined. Problems to be investigated include 1) microvascular red cell and plasma flow distribution in series and parallel coupled vessels, 2) effects of filtration and absorption across the capillary membrane on red cell plasma flow, 3) relationships of RBC concentration on RBC and plasma velocity, 4) quantitation in parallel circuits of flow velocity and length effects on heterogeneity, 5) microvascular volume distribution, 6) quantitation of longitudinal gradient of capillary permeability and interstial movement of macromolecules, and 7) reactivity of different sized pre- and post-capillary microvessels. Assessments will be made in several orders of magnitude of arterioles, capillaries and venules in the cat mesentery and rat cremaster muscle microcirculations. Data will be related to changes on the whole organ level. Indicator dilution techniques (FITC-dextran and sulphemoglobin-RBC dispersion) will be used to assess plasma and red cell flow and volume distribution. Measurements of central and microvascular pressure, RBC velocity and microvessel dimension changes will be made. Comparison of changes in vessel volume as calculated from determinations of volume and length with indicator mean transit time volumes will be made during vasomotor responses to various stimuli. Changes in capillary permeability with various experimental procedures will be quantitated using fluorescein labeled dextrans or proteins of different molecular weights. The effects of intraluminal pressure and radius on vessel responses to standard stimuli will also be evaluated with emphasis on the influences upon resistance to blood flow. An understanding of the interrelationships between the various physiological parameters described in this proposal are basic to not only the normal situation but also of altered function and pathological conditions. Quantitative evaluation of altered vasomotor function and reactivity during processes such as hypertension, endotoxin and hemorrhagic shock and congestive failure of the circulation will be possible.